rs4234218

Positions:

• chr3-124242363-G-C
• chr3-124242363-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.263+7420G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,170 control chromosomes in the GnomAD database, including 9,208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9208 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.263+7420G>C		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.263+7420G>C		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51464 AN: 152052 Hom.: 9205 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51484 AN: 152170 Hom.: 9208 Cov.: 33 AF XY: 0.340 AC XY: 25272 AN XY: 74384

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.329

Alfa AF: 0.208 Hom.: 463

Bravo AF: 0.328

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4234218; hg19: chr3-123961210;